Tunably strained metallacycles enable modular differentiation of aza-arene C–H bonds

Abstract

The precise activation of C–H bonds will eventually provide chemists with transformative methods to access complex molecular architectures. Current approaches to selective C–H activation relying on directing groups are effective for the generation of five-membered, six-membered and even larger ring metallacycles but show narrow applicability to generate three- and four-membered rings bearing high ring strain. Furthermore, the identification of distinct small intermediates remains unsolved. Here, we developed a strategy to control the size of strained metallacycles in the rhodium-catalysed C−H activation of aza-arenes and applied this discovery to tunably incorporate the alkynes into their azine and benzene skeletons. By merging the rhodium catalyst with a bipyridine-type ligand, a three-membered metallacycle was obtained in the catalytic cycle, while utilizing an NHC ligand favours the generation of the four-membered metallacycle. The generality of this method was demonstrated with a range of aza-arenes, such as quinoline, benzo[f]quinolone, phenanthridine, 4,7-phenanthroline, 1,7-phenanthroline and acridine. Mechanistic studies revealed the origin of the ligand-controlled regiodivergence in the strained metallacycles.

Regiodivergent Metal-Catalyzed Oxidative Alkynylation of 2-Arylthiazoles with Terminal Alkynes under Air Conditions

“…The reliable and powerful construction of these molecules is the Pd/Cu-catalyzed cross-coupling of aryl halides with terminal alkynes, which is called Sonogashira coupling (Scheme b, Path I) . In recent years, a promising strategy for the metal-catalyzed direct C–H alkynylation of arenes/heteroarenes with alkynyl halides or pseudohalides has been gaining much attention due to the advantage of offering a more straightforward access to expected compounds by avoiding prefunctionalization of starting molecules in fewer steps (Scheme b, Path II) . To be noted, the direct oxidative C–H alkynylation or cross-dehydrogenative coupling between arenes/heteroarenes and terminal alkynes via C–H bond cleavage of both substrates is a step and atom economical procedure since the preactivation step is precluded at both coupling partners (Scheme b, Path III).…”

Regiodivergent C–H alkynylation of 2-arylthiazoles switched by RuII and PdII catalysis

“…12 Subsequently, Shi and co-workers reported an efficient protocol for regiodivergent C–H alkynylation of quinolones enabled by tunably strained metallacycles under monomeric rhodium catalysts. 13…”